1. Field of the Invention
This invention relates to triazenyl derivatives of 1-alkyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids as antibacterial agents and to a process for their preparation.
2. Description of the Prior Art
In a paper entitled "Coupling Reactions of Aminoquinolines with Benzenediazonium Chloride. A Study of Orientation in the Quinoline Ring", Renshaw et al. [J. Am. Chem. Soc. 61, 3322 (1939)] show that the reaction of benzenediazonium chloride with 7-aminoquinoline yields 7-amino-8-phenylazoquinoline, whereas the same coupling reaction with 2-aminoquinoline and 3-aminoquinoline result respectively in the formation of "2-benzenediazoaminoquinoline" and "3-benzenediazoaminoquinoline", respectively, "diazoamino" being the same as "triazeno" or, as used hereinbelow, triazenyl.
Adams et al. [J. Chem. Soc. 1949, pp. 3181ff] converted 3-aminoquinoline into its diazonium salt by reaction with hydrochloric acid and an aqueous solution of sodium nitrite and then reacted with diazonium salt with dimethylamine to produce 3,3-dimethyl-1-(3'-quinolinyl)triazene.
Rondestvedt and Davis reported [J. Org. Chem. 22, 200 (1957)] the preparation of over 50 1-aryl-3,3-dialkyltriazenes "by coupling a diazonium salt with a secondary (occasionally primary) amine in basic medium", most of the compounds being those where "aryl" was phenyl or substituted-phenyl and including one quinoline compound, namely, 3,3-dimethyl-1-(3'-quinolinyl)triazene, the same compound that had been reported earlier by Adams et al., supra. It is not clear from the article whether 3,3-dimethyl-1-(3'-quinolinyl)triazene was found to be active or inactive in the preliminary anti-cancer screen. The 3,3-dimethyl-1-(3'-quinolinyl)triazene is characterized as follows: "Explodes during microanalysis"; "Crude product is very unstable"; "Must be filtered and washed throughly with ice water, then recrystallized while wet"; "it is allowed to dry while crude, it decomposes in a puff of smoke"; "The purified material darkens rapidly, but less dramatically, on storage".
Lin et al. [ABSTRACT OF PAPERS, 173rd ACS Meeting, New Orleans, La., Mar. 20-25, 1977, Paper No. 74, Division of Medicinal Chemistry] synthesized various 6(7 or 8)-halo-4-(3,3-dimethyl-1-triazeno)quinolines by diazotization of the appropriate 4-amino-6(7 or 8 )quinoline in fluoboric acid at -5.degree. C. followed by coupling with dimethylamine. This abstract reported "Preliminary results indicate that 6-chloro, 7-chloro, and 8-chloro-4-(3,3-dimethyl-1-triazeno)quinolines are active (as potential anti-tumor agents), prolonging the life-span of mice bearing i.p. implanted P-388 tumor from 10 days for control animals to 16-18 days for treated mice at an i.p. dosage of 30 mg/kg". The 6-iodo, 6-bromo, 7-bromo, and 8-bromo analogs were reported as inactive against this tumor up to 40 mg/kg and the 6-bromo, 8-bromo and 8-chloro derivatives were reported to be active against mouse L-1210 leukemia, "increasing the life-span by 50%, 65% and 65% respectively at 30 to 40 mg/kg dosage".